Most Graft Failure Causes Identifiable

Only 10% are idiopathic, suggesting that the diagnosis of chronic allograft nephropathy is overused.

TORONTO—Study results confirm the wisdom of an expert consensus that nephrologists should not overuse the diagnosis of chronic allograft nephropathy (CAN).

A review of all kidney transplants performed at the Mayo Clinic in Rochester, Minn., between January 1, 1996, and July 1, 2006 revealed that only 10% of kidney graft failures were idiopathic.

“Most cases of kidney graft loss can be attributed to a specific cause,” said co-lead investigator Ziad El-Zoghby, MD, a nephrology fellow at the Mayo Clinic. “Glomerular pathologies represent the largest proportion of death-censored graft failures, while immunologic mechanisms also are responsible for many cases.”

This view closely mirrors the conclusions of the Banff '05 Meeting Report, which called for the elimination of the use of the term chronic allograft nephropathy (Amer J Transplant. 2007;7:518-526). The report's authors noted that “the use of the non-specific term ‘CAN' has tended to undermine recognition of morphological features enabling diagnosis of specific causes of chronic graft dysfunction. For example, many allograft recipients are hypertensive, which can lead to chronic allograft injury with fibrosis.”

One of the report's authors, Robert Colvin, MD, Benjamin Castleman Distinguished Professor of Pathology at Harvard Medical School in Boston, told Renal & Urology News that the new Mayo Clinic study is “valid and important … because if we know the cause of the graft injury earlier, specific therapy can be instituted which may prevent some of the graft loss.”

The Mayo Clinic team focused on the 143 cases of death-censored graft failure that occurred in the study period. Glomerular pathology was identified in 54 cases (38%), fibrosis/atrophy in 44 (31%), medical causes such as infection, recurrent diseases such as scleroderma, graft lymphoma or heart failure in 22 (15%), acute rejection in 18 (13%), and unknown causes in five (3%).

The team also probed into each of the classes of failure and found, for example, that recurrent disease and transplant glomerulopathy were each responsible for 41% of the glomerular causes of graft failure, and polyoma virus nephropathy and recurrent rejections each accounted for 25% of the failures associated with fibrosis/atrophy. Only nine (6%) of the fibrosis/atrophy cases were idiopathic (6% of all the grafts lost).

Adding the five cases for which the cause was unknown, the cause of graft failure is identifiable in 90% of the cases and should not be attributed to CAN.